Prognostic Significance of TMPRSS2-ERG Fusion Gene in Prostate Cancer

Kulda, Vlastimil; Topolčan, Ondřej; Kučera, Radek; Kripnerová, Michaela; Srbecka, Kristyna; Hora, Milan; O, Hes; Klečka, Jiří; Babuška, Václav; Roušarová, Milena; Benson, Veronika; Pešta, Martin

doi:10.21873/anticanres.11037

Cited by 25 publications

(25 citation statements)

References 26 publications

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“…[1,3] The prognostic and predictive value of TMPRSS2-ERG fusions is still under active investigation; however, some studies have suggested an association of the fusion gene with higher recurrence risk and possibly even increased risk of prostate cancer-related death. [4-6]…”

Section: Introductionmentioning

confidence: 99%

TMPRSS2-ERG Fusions Unexpectedly Identified in Men Initially Diagnosed With Nonprostatic Malignancies

Lara

Heilmann²,

Elvin³

et al. 2017

JCO Precision Oncology

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Background TMPRSS2-ERG gene fusions are frequently found in prostate cancer and are pathognomomic for prostatic origin. In a series of cancer cases assayed with comprehensive genomic profiling (CGP) in the course of clinical care, we reviewed the frequency of TMPRSS2-ERG fusions in patient tumors of various histologic subtypes. Methods Frequency of TMPRSS2-ERG fusions was determined in comprehensive genomic profiles from 64,263 cancer cases submitted to Foundation Medicine to assess genomic alterations suggesting benefit from targeted therapy. Genomic results from an index case of prostate cancer that underwent evolution from adenocarcinoma to pure squamous cell carcinoma are presented. Results TMPRSS2-ERG fusions were identified for 0.86% (250/29030) of male patients and not found for female patients (0/35233). TMPRSS2-ERG fusions were detected in six tumors that were classified as squamous carcinoma, five of which were of unknown primary site. The index case is a patient with a large left retrovesical mass diagnosed as squamous carcinoma by morphologic examination and a history of Gleason 9 prostate cancer with prior prostatectomy and salvage radiation therapy. TMPRSS2-ERG was detected by genomic profiling in the squamous cell tumor, the primary adenocarcinoma of the prostate, and in a metachronous prostatic adenocarcinoma metastasis. Based on these results, the patient received androgen deprivation therapy. A phylogenetic tree demonstrating clonal and histopathologic evolution of prostate cancer in the index patient was constructed. Conclusions In this large CGP dataset, TMPRSS2-ERG fusion was seen in ~30% of prostate cancers regardless of histologic type; the fusion was on occasion detected in advanced cancers not initially carrying a diagnosis of prostate carcinoma. CGP of advanced cancers in men may reveal prostatic origin by detection of the pathognomomic TMPRSS2-ERG fusion gene.

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Section: Introductionmentioning

confidence: 99%

TMPRSS2-ERG Fusions Unexpectedly Identified in Men Initially Diagnosed With Nonprostatic Malignancies

Lara

Heilmann²,

Elvin³

et al. 2017

JCO Precision Oncology

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“…For PCa, carcinogenesis and the mechanisms affecting the progression and prognosis are multistep processes [21]. Although the previous reports have shown that many factors including lncRNA HCG11, miR-129, as well as TMPRSS2-ERG fusion gene have affected the development and prognosis of PCa [22][23][24], the prediction and diagnosis of PCa patients was still poor. Thus it is important to nd a novel biomarker to improve the diagnostic e ciency of PCa.…”

Section: Discussionmentioning

confidence: 99%

SOX9 stands for a bio-marker for prostate cancer detection

Tao

Gao

et al. 2020

Preprint

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Background Prostate cancer is one of common cancers around the world, and in our country the incidence and mortality of PCa are both increasing. More and more reports have revealed that SOX9 is involved in various human cancers. In this study, we aimed to explore the relationship between SOX9 expression and diagnostic value of PCa patients. Methods In this study, quantitative real-time PCR (qRT-PCR) was performed to determine the expression of SOX9 of the 131 PCa patients and 74 healthy volunteers. And receiver operating characteristic (ROC) curve was used to determine the diagnostic value of SOX9 for PCa patients. Results The results of qRT-PCR showed that the expression of serum SOX9 in PCa patients was higher than that in healthy controls (P < 0.05). And the expression of SOX9 was significantly associated with PSA (P = 0.001), differentiation (P = 0.000), and lymph node metastasis (P = 0.000). Besides, the area under the ROC curve (AUC) was 0.966 with the sensitivity of 93.2% and specificity of 87.8% respectively. The optimal cutoff value of SOX9 was 2.34. Conclusions Our results found that SOX9 is a novel oncogene for PCa, and may be a novel and effective biomarker for the diagnosis of patients with PCa.

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“…72 ERG rearrangements and over-expression define the largest of the molecular classes of PC based on molecular oncogenic drivers and has been repeatedly associated with accelerated disease progression and worse prognosis. 73-74 More recently, many reports have correlated response to treatment to ERG expression, which became a compelling biomarker to investigate clinically.…”

Section: Ctc As Source Of Tumor Tissue For Biomarker Investigationmentioning

confidence: 99%

Using circulating tumor cells to advance precision medicine in prostate cancer

Galletti

Worroll

Nanus

et al. 2017

JCMT

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The field of CTC enrichment has seen many emerging technologies in recent years, which have resulted in the identification and monitoring of clinically relevant, CTC-based biomarkers that can be analyzed routinely without invasive procedures. Several molecular platforms have been used to investigate the molecular profile of the disease, from high throughput gene expression analyses down to single cell biological dissection. The established presence of CTC heterogeneity nevertheless constitutes a challenge for cell isolation as the several subpopulations can potentially display different molecular characteristics; in this scenario, careful consideration must be given to the isolation approach, whereas methods that discriminate against certain subpopulations may result in the exclusion of CTCs that carry biological relevance. In the context of prostate cancer (PC), CTC molecular interrogation can enable longitudinal monitoring of key biological features during treatment with substantial clinical impact, as several biomarkers could predict tumor response to AR signaling inhibitors (abiraterone, enzalutamide) or standard chemotherapy (taxanes). Thus, CTCs represent a valuable opportunity to personalize medicine in current clinical practice.

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Prognostic Significance of TMPRSS2-ERG Fusion Gene in Prostate Cancer

Abstract: A combination of high preoperative serum PSA and high expression of TMPRSS2-ERG could be promising in distinguishing those tumors that are aggressive and life-threatening.

Cited by 25 publications

References 26 publications

TMPRSS2-ERG Fusions Unexpectedly Identified in Men Initially Diagnosed With Nonprostatic Malignancies

TMPRSS2-ERG Fusions Unexpectedly Identified in Men Initially Diagnosed With Nonprostatic Malignancies

SOX9 stands for a bio-marker for prostate cancer detection

Using circulating tumor cells to advance precision medicine in prostate cancer

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